256 Ways to Be Depressed (and Finding a Path Out of It)

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One of the most important things we’ve learned about the brain recently is that there is not necessarily a great deal of difference between disorders that are clearly organic and those we’ve thought of as psychological illnesses. Brain disorders may manifest themselves either physically or emotionally (or both), but in so many cases we can trace the origin to a biological cause. A brain tumor may cause headaches, double vision – or changes in mood. A chemical imbalance can cause someone to fidget, lose their appetite – or develop bipolar disorder. Fortunately it’s becoming more widely understood that “mental health” conditions are really just “health” conditions.

One of the most common brain disorders is clinical depression—and by that I don’t mean the normal sadness or grief we all feel after a negative experience such as the death of a loved one or the end of a relationship. True clinical depression is profound and life-altering, and it often requires medical treatment. It’s a complicated condition, but science has agreed that there are nine signs of clinical depression:

A patient reporting any five of these nine symptoms is considered clinically depressed – that means there are 256 possible combinations of symptoms that can lead to a diagnosis of depression. In some patients this is self-limiting and mild, and in others it is persistent and severe. It’s important not to allow depression to become prolonged, since the state of being depressed has been shown to lead to physical changes in the brain—such as inflammation, or even brain shrinkage—making this a vicious cycle: A disturbance in the brain can make someone depressed, then by virtue of being depressed that person can experience further damage to the brain.

I recently spoke about depression with Dr. Conor Liston for an episode of my podcast, This Is Your Brain. Dr. Liston is an associate professor of neuroscience and psychiatry here at Weill Cornell Medicine, and he is also conducting research to advance our understanding of the neurobiology of depression and treating psychiatric disorders. Among other things, we talked about the four distinct subtypes of depression:

Seasonal: I lived in Stockholm for a year, so I have firsthand experience with this one. By the time March came around, after those long winter months in which the sun never came up, I had a good sense of what seasonal depression is. Even a healthy person can find themselves feeling down when it’s dark all the time; in someone with seasonal depression the symptoms can impact daily function to the point where medical intervention is needed.

Melancholic: This is the “black dog” that haunted Winston Churchill and Abraham Lincoln. We often refer to temporary sadness as melancholy, but true melancholic depression can be particularly debilitating. A person with this subtype is probably what we all think of when we picture depression: poor mood, sadness, low affect.

Agitated: Not everyone with depression has a low affect. Those with the agitated subtype of depression can be, as the name suggests, angry and prone to outbursts. They are often irritable and restless – they may not appear to be depressed since they don’t show signs of sadness, but the agitated subtype is very much a form of depression.

Atypical: Those with atypical depression can be more difficult to diagnose, since their mood can be variable and can even improve temporarily in response to good news or experiences. But atypical depression is still depression – patients may report a leaden feeling in their limbs, and a sense of lethargy.

Listen to the podcast episode with Dr. Liston:

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One of the biggest difficulties faced by patients with depression and their doctors is that identifying the subtype doesn’t often help with choosing the best treatment – that’s still very much a trial-and-error process. Doctors may first prescribe an SSRI (a selective serotonin reuptake inhibitor) – that’s a class of drugs that was initially tested for use on patients with tuberculosis, and researchers found that the TB patients tended to experience improvements in mood while taking it. That was a lucky accident that led to an effective treatment for depression. SSRIs have become very popular because they usually don’t have the negative side effects patients experience with other classes of medication, including indigestion, weight gain, loss of libido, even suicidal ideation.

There are some very interesting new treatment options on the horizon, and Dr. Liston is a leading researcher in the field. Please do listen to this podcast episode for more information about current medication choices, the degree to which genetics play a role in depression, and how psychiatrists work with patients to find the best combination of drugs and talk therapy.